A Study to Evaluate the Effect of Ibrutinib on the Pharmacokinetics of Oral Contraceptives, CYP2B6, and CYP3A4 Substrates in Female Participants With B Cell Malignancy

Sponsor
Janssen Research & Development, LLC
Study ID
NCT03301207
Phase
PHASE1
Status
Completed

Conditions

  • Leukemia, Lymphocytic, Chronic, B-Cell

Eligibility Criteria

Sex
FEMALE
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Ibrutinib — DRUG
    Ibrutinib capsule (at dose of 420 or 560 mg) will be taken orally QD.
  • OC: Ethinylestradiol (EE) 30 mcg and Levonorgestrel (LN) 150 mcg — DRUG
    Single dose of oral contraceptives (OC) (1 tablet containing 30 mcg EE and 150 mcg LN) will be taken orally on Study Days 1 and 22.
  • Bupropion — DRUG
    Bupropion 75 mg tablet as a part of CYP cocktail will be taken on Study Days 3 and 24.
  • Midazolam — DRUG
    Midazolam 2 mg (1 milliliter \[mL\]) oral solution will be taken on Study Days 3 and 24 (as a part of CYP cocktail) and on Study Day 8 (alone).

Study Details

The main purpose of this study is to evaluate the effects of repeat dosing of ibrutinib on the single-dose pharmacokinetics (PK) of oral contraceptives (OC - ethinylestradiol \[EE\] and levonorgestrel \[LN\]), the cytochrome P450 (CYP)2B6 probe bupropion and the CYP3A4 probe midazolam; and to evaluate the effects of single-dose ibrutinib on the single-dose PK of the CYP3A4 probe midazolam in female participants with B cell malignancy.

Key Dates

Start date
Oct 20, 2017
Status verified
Nov 2019
Primary completion
Jul 17, 2018
Completion
Dec 4, 2018

Study Design

Enrollment
25 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER

Arms

  • Experimental: Ibrutinib + Oral Contraceptives + Probe Drugs (CYP)
    Pre-treatment Phase: Participants will receive a single dose of oral contraceptive (OC) consisting of ethinylestradiol (EE) 30 microgram (mcg) and levonorgestrel (LN) 150 mcg on Study Day 1, and probe drugs (CYP) consisting of bupropion 75 milligram (mg) and midazolam 2 mg on Study Day 3, followed by a washout period from Study Days 4 to 7. Treatment Phase: Participants will receive ibrutinib 560 mg (4\*140 mg capsules) once daily (QD) on Days 8 to 26 along with midazolam 2 mg once orally on Study Day 8 (Cycle 1 Day 1), OC once orally on Study Day 22 (Cycle 1 Day 15; EE and LN), and bupropion 75 mg and midazolam 2 mg once orally on Study Day 24 (Cycle 1 Day 17). From Study Day 27 (Cycle 1 Day 20) and onwards participants will continue oral treatment with ibrutinib 420 mg (3\*140 mg capsules) or 560 mg QD (depending on the subtype of B-cell malignancy) up to the end of Cycle 6 (each cycle will consist of 28 days).

Primary Outcome Measure

Maximum Observed Plasma Concentration (Cmax) of Ethinylestradiol (EE) and Levonorgestrel (LN) When Co-administered With Repeat Doses of Ibrutinib Compared to Administration Alone [ Time Frame: Days 1 and 22: predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, and 72 hours (h) post-dose ]

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